Improvement of inflammatory and toxic stress biomarkers by silymarin in a murine model of type one diabetes mellitus

Type 1 diabetes mellitus (T1DM) is characterized by an impairment of the insulin-secreting beta cells with an immunologic base. Inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and free radicals are believed to play key roles in destruction of pancreatic β cells. The present study was designed to investigate the effect of Silybum marianum seed extract (silymarin), a combination of several flavonolignans with immunomodulatory, anti-oxidant, and anti-inflammatory potential on streptozotocin (STZ)-induced T1DM in mouse. Experimental T1DM was induced in male albino mice by IV injection of multiplelow- doses of STZ for 5 days. Seventy-two male mice in separate groups received various doses of silymarin (20, 40, and 80 mg/kg) concomitant or after induction of diabetes for 21 days. Blood glucose and pancreatic biomarkers of inflammation and toxic stress (IL-1β, TNF-α, myeloperoxidase, lipid peroxidation, protein oxidation, thiol molecules, and total antioxidant capacity) were determined. Silymarin treatment reduced levels of inflammatory cytokines such as TNF-α and IL-1β and oxidative stress mediators like myeloperoxidase activity, lipid peroxidation, carbonyl and thiol content of pancreatic tissue in an almost dose dependent manner. No marked difference between the prevention of T1DM and the reversion of this disease by silymarin was found. Use of silymarin seems to be helpful in T1DM when used as pretreatment or treatment. Benefit of silymarin in human T1DM remains to be elucidated by clinical trials.     

VARIATION IN THE STRENGTH AND SOFTNESS OF SELECTION ON DELETERIOUS MUTATIONS

Deleterious alleles constantly enter populations through mutation. Understanding the nature of selection against such alleles is required to assess their impact on populations. In a subdivided population, two distinct aspects of selection are important: the strength and softness of selection. Using Drosophila melanogaster, we estimated both aspects of selection for each of eight loci across two environments. These data allow us to test conflicting predictions about the factors affecting the softness of selection. First, we show that the softness of selection is not determined by ecological conditions alone. Second, we find that resource limitation makes selection stronger but does not make it softer. Third, we find that wild‐type individuals tend to benefit more than mutants from being reared with competitors of low genetic quality. This means that selection is effectively “harder” on mutants than wild types. A model is presented showing that the sensitivities of mutants and wild types to local competitors differentially affect equilibrium mutation frequency and measures of load.     

Iodine deficiency and subclinical hypothyroidism are common in cystic fibrosis patients

BackgroundDisorders of thyroid function have been inconsistently described in cystic fibrosis (CF) patients and in CF transmembrane regulator protein knockout animals. The literature lacks reports on iodine status of CF individuals. We hypothesize, that iodine deficiency is common in CF and account for abnormal thyroid function in CF patients.MethodsWe investigated 129 children, adolescents, and adults with CF, who were living in the northern part of Bavaria/Germany. Malnutrition and lung function were analyzed. Urinary iodine excretion, TSH (thyroid-stimulating hormone), and ft4 (free thyroxine) were measured and set in relation to population-based, age-adjusted reference ranges.ResultsSubclinical hypothyroidism (normal fT4, elevated TSH) was found in 11.6% of subjects, and iodine deficiency in 83.7%. No correlations were found with age, BMI, status of malnutrition, or lung function.ConclusionDramatic iodine deficiency was found in our cohort of CF patients. This condition can cause subclinical hypothyroidism; therefore, an individual iodine supplementation program is necessary and should be started immediately.     

Fine-Tuning of the Cellular Signaling Pathways by Intracellular GTP Levels

It has become increasingly evident that among purine nucleotides, guanine based nucleotides specially guanosine-5′-triphosphate (GTP) serve as an important and independent regulatory factors for development and diverse cellular functions such as differentiation, metabolism, proliferation and survival in multiple tissues. In this brief review, it has been provided selective outline related to delicate regulation of signaling pathways by guanosine based nucleotides as intracellular signaling molecules. Although the exact mode of action of theses nucleotides in many biological processes and signaling pathways is still elusive, it has become well clear that intracellular guanosine based nucleotides content rather than adenosine based nucleotides could modulate the intensity and duration of signaling which ultimately impact on cell’s fate. It opens an entirely new perspective for developing new and potential therapeutic strategies to combat diseases like cancer, hypoxia, etc.     

Immobilization of acetylcholinesterase in nanofibrous PVA/BSA membranes by electrospinning

Electrospinning, a simple and versatile method to fabricate nanofibrous supports, has attracted continuous attention in the field of enzyme immobilization. In this study, acetylcholinesterase (AChE) has been successfully immobilized in PVA nanofibers via electrospinning of a mixture of AChE, BSA as an enzyme stabilizing additive and PVA. The maximum activity recovery of immobilized AChE was about 40%. In comparison with free enzyme, the immobilized AChE showed improved stability while retaining a considerable amount of activity at lower pH values. Moreover, the immobilized AChE retained >34% of its initial activity when stored at 30°C for 100 days and retained 70% of its initial activity after ten consecutive reactor batch cycles.     

Benefit of nicorandil using an immunologic murine model of experimental colitis

Inflammatory bowel disease (IBD) is a chronic inflammatory condition with an unknown etiology. Nicorandil, a potassium channel opener, has been used for many years for the treatment of angina. Recently, it has been shown that nicorandil possesses some novel traits such as anti-apoptotic, gastroprotective, free radical scavenging, and anti-inflammatory properties. Therefore, we set out to examine the possible beneficial effect of nicorandil in a rat model of IBD. Colitis was induced by rectal administration of 2,4,6-trintrobenzene sulphonic acid (TNBS) into rats. Groups of animals used in this study were sham, control, and exposure to dexamethasone, nicorandil, glibenclamid (a pure adenosine triphosphate sensitive potassium channel (KATP) blocker), or nicorandil plus glibenclamid. Drugs were administered by gavage and animals were sacrificed after 7 days. Biochemical markers, including TNF-α and IL-1β, ferric reducing/antioxidant power (FRAP), myeloperoxidase (MPO) activity and thiobarbitoric acid-reactive substance (TBARS), were measured in the homogenate of colonic tissue. Results indicate that nicorandil significantly reduces macroscopic and histological damage induced by TNBS. Nicorandil diminishes MPO activity and levels of TBARS, TNF-∢, and IL-1β in damaged colonic tissue with a concomitant increase in FRAP value (P<0.01). These effects were not reversed by coadministration of glibenclamide. In conclusion, nicorandil is able to ameliorate experimental IBD with a dose in which it does not show any anti-hypertensive effect, and the mechanism of which is partially or totally independent from KATP channels. It is hypothesized that nitric oxide donation and free-radical scavenging properties of nicorandil upregulate endothelial nitric oxide synthase may be responsible for this phenomenon. These findings suggest that nicorandil can be useful in treatment of IBD, although further investigations are needed to elucidate the mechanisms involved.     

A global treatments for coronaviruses including COVID-19

In late December 2019 in Wuhan, China, several patients with viral pneumonia were identified as 2019 novel coronavirus (2019-nCoV). So far, there are no specific treatments for patients with coronavirus disease-19 (COVID-19), and the treatments available today are based on previous experience with similar viruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Influenza virus. In this article, we have tried to reach a therapeutic window of drugs available to patients with COVID-19. Cathepsin L is required for entry of the 2019-nCoV virus into the cell as target teicoplanin inhibits virus replication. Angiotensin-converting-enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. In patients with COVID-19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality. Neuraminidase inhibitors such as oseltamivir, peramivir, and zanamivir are invalid for 2019-nCoV and are not recommended for treatment but protease inhibitors such as lopinavir/ritonavir (LPV/r) inhibit the progression of MERS-CoV disease and can be useful for patients of COVID-19 and, in combination with Arbidol, has a direct antiviral effect on early replication of SARS-CoV. Ribavirin reduces hemoglobin concentrations in respiratory patients, and remdesivir improves respiratory symptoms. Use of ribavirin in combination with LPV/r in patients with SARS-CoV reduces acute respiratory distress syndrome and mortality, which has a significant protective effect with the addition of corticosteroids. Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID-19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids.     

Evaluation of Exposure to Radiofrequency Electromagnetic Fields from Smart Utility Meters operating at 868 MHz

Power density and duty factor values were measured around smart utility meters operating at 868 MHz under laboratory-controlled conditions. The maximum 6-min averaged exposure recorded was 0.1 mWm⁻², which is less than 0.0024% of the corresponding 1998 ICNIRP general public reference level. Duty factors measured were less than 2.8%. This study found that the exposure contribution from Zigbee smart meter devices operating at 868 MHz is generally lower than, if not similar to, those operating at 2.4 GHz. © 2023 Crown copyright. Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society.